Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury
Spinal cord injury (SCI) is a severe disease of the nervous system that causes irreparable damage and loss of function, for which no effective treatments are available to date. Engineered extracellular vesicles (EVs) carrying therapeutic molecules hold promise as an alternative SCI therapy depending...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-05-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22004753 |
| _version_ | 1811160196586668032 |
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| author | Yuluo Rong Zhuanghui Wang Pengyu Tang Jiaxing Wang Chengyue Ji Jie Chang Yufeng Zhu Wu Ye Jianling Bai Wei Liu Guoyong Yin Lipeng Yu Xuhui Zhou Weihua Cai |
| author_facet | Yuluo Rong Zhuanghui Wang Pengyu Tang Jiaxing Wang Chengyue Ji Jie Chang Yufeng Zhu Wu Ye Jianling Bai Wei Liu Guoyong Yin Lipeng Yu Xuhui Zhou Weihua Cai |
| author_sort | Yuluo Rong |
| collection | DOAJ |
| description | Spinal cord injury (SCI) is a severe disease of the nervous system that causes irreparable damage and loss of function, for which no effective treatments are available to date. Engineered extracellular vesicles (EVs) carrying therapeutic molecules hold promise as an alternative SCI therapy depending on the specific functionalized EVs and the appropriate engineering strategy. In this study, we demonstrated the design of a drug delivery system of peptide CAQK-modified, siRNA-loaded EVs (C-EVs-siRNA) for SCI-targeted therapy. The peptide CAQK was anchored through a chemical modification to the membranes of EVs isolated from induced neural stem cells (iNSCs). CCL2-siRNA was then loaded into the EVs through electroporation. The modified EVs still maintained the basic properties of EVs and showed favorable targeting and therapeutic effects in vitro and in vivo. C-EVs-siRNA specifically delivered siRNA to the SCI region and was taken up by target cells. C-EVs-siRNA used the inherent anti-inflammatory and neuroreparative functions of iNSCs-derived EVs in synergy with the loaded siRNA, thus enhancing the therapeutic effect against SCI. The combination of targeted modified EVs and siRNA effectively regulated the microenvironmental disturbance after SCI, promoted the transformation of microglia/macrophages from M1 to M2 and limited the negative effects of the inflammatory response and neuronal injury on functional recovery in mice after SCI. Thus, engineered EVs are a potentially feasible and efficacious treatment for SCI, and may also be used to develop targeted treatments for other diseases. |
| first_indexed | 2024-04-10T05:53:32Z |
| format | Article |
| id | doaj.art-fbfdf5bc8d454119bc9b1cd2763f9c7a |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-10T05:53:32Z |
| publishDate | 2023-05-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-fbfdf5bc8d454119bc9b1cd2763f9c7a2023-03-04T04:23:33ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-05-0123328342Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injuryYuluo Rong0Zhuanghui Wang1Pengyu Tang2Jiaxing Wang3Chengyue Ji4Jie Chang5Yufeng Zhu6Wu Ye7Jianling Bai8Wei Liu9Guoyong Yin10Lipeng Yu11Xuhui Zhou12Weihua Cai13Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China; Corresponding author. Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China; Corresponding author. Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China; Corresponding author. Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.Spinal cord injury (SCI) is a severe disease of the nervous system that causes irreparable damage and loss of function, for which no effective treatments are available to date. Engineered extracellular vesicles (EVs) carrying therapeutic molecules hold promise as an alternative SCI therapy depending on the specific functionalized EVs and the appropriate engineering strategy. In this study, we demonstrated the design of a drug delivery system of peptide CAQK-modified, siRNA-loaded EVs (C-EVs-siRNA) for SCI-targeted therapy. The peptide CAQK was anchored through a chemical modification to the membranes of EVs isolated from induced neural stem cells (iNSCs). CCL2-siRNA was then loaded into the EVs through electroporation. The modified EVs still maintained the basic properties of EVs and showed favorable targeting and therapeutic effects in vitro and in vivo. C-EVs-siRNA specifically delivered siRNA to the SCI region and was taken up by target cells. C-EVs-siRNA used the inherent anti-inflammatory and neuroreparative functions of iNSCs-derived EVs in synergy with the loaded siRNA, thus enhancing the therapeutic effect against SCI. The combination of targeted modified EVs and siRNA effectively regulated the microenvironmental disturbance after SCI, promoted the transformation of microglia/macrophages from M1 to M2 and limited the negative effects of the inflammatory response and neuronal injury on functional recovery in mice after SCI. Thus, engineered EVs are a potentially feasible and efficacious treatment for SCI, and may also be used to develop targeted treatments for other diseases.http://www.sciencedirect.com/science/article/pii/S2452199X22004753Extracellular vesiclesSpinal cord injurysiRNAMicroglia/macrophages polarizationInduced neural stem cells |
| spellingShingle | Yuluo Rong Zhuanghui Wang Pengyu Tang Jiaxing Wang Chengyue Ji Jie Chang Yufeng Zhu Wu Ye Jianling Bai Wei Liu Guoyong Yin Lipeng Yu Xuhui Zhou Weihua Cai Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury Bioactive Materials Extracellular vesicles Spinal cord injury siRNA Microglia/macrophages polarization Induced neural stem cells |
| title | Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury |
| title_full | Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury |
| title_fullStr | Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury |
| title_full_unstemmed | Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury |
| title_short | Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury |
| title_sort | engineered extracellular vesicles for delivery of sirna promoting targeted repair of traumatic spinal cord injury |
| topic | Extracellular vesicles Spinal cord injury siRNA Microglia/macrophages polarization Induced neural stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X22004753 |
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